3D8H

Crystal structure of phosphoglycerate mutase from Cryptosporidium parvum, cgd7_4270

Summary for 3D8H

• Entry DOI: 10.2210/pdb3d8h/pdb
• Descriptor: Glycolytic phosphoglycerate mutase (2 entities in total)
• Functional Keywords: structural genomics, malaria, cryptosporidium, glycolysis, isomerase, structural genomics consortium, sgc
• Biological source: Cryptosporidium parvum
• Total number of polymer chains: 2
• Total formula weight: 60411.41

Authors

Wernimont, A.K.,Lew, J.,Wasney, G.,Alam, Z.,Kozieradzki, I.,Cossar, D.,Schapiro, M.,Bochkarev, A.,Arrowsmith, C.H.,Bountra, C.,Wilkstrom, M.,Edwards, A.M.,Hui, R.,Artz, J.D.,Hills, T.,Structural Genomics Consortium (SGC) (deposition date: 2008-05-23, release date: 2008-07-15, Last modification date: 2023-08-30)

Primary citation

Hills, T.,Srivastava, A.,Ayi, K.,Wernimont, A.K.,Kain, K.,Waters, A.P.,Hui, R.,Pizarro, J.C.
Characterization of a new phosphatase from Plasmodium.
Mol.Biochem.Parasitol., 179:69-79, 2011

PubMed Abstract: Plasmodium falciparum malaria is the most important parasitic disease worldwide, responsible for an estimated 1 million deaths annually. Two P. falciparum genes code for putative phosphoglycerate mutases (PGMases), a widespread protein group characterized by the involvement of histidine residues in their catalytic mechanism. PGMases are responsible for the interconversion between 2 and 3-phosphoglycerate, an intermediate step in the glycolysis pathway. We have determined the crystal structures of one of the P. falciparum's PGMases (PfPGM2) and a functionally distinct phosphoglycerate mutase from Cryptosporidium parvum, a related apicomplexan parasite. We performed sequence and structural comparisons between the two structures, another P. falciparum enzyme (PfPGM1) and several other PGM family members from other organisms. The comparisons revealed a distinct conformation of the catalytically active residues not seen in previously determined phosphoglycerate mutase structures. Furthermore, characterization of their enzymatic activities revealed contrasting behaviors between the PfPGM2 and the classical cofactor-dependent PGMase from C. parvum, clearly establishing PfPGM2 as a phosphatase with a residual level of mutase activity. Further support for this function attribution was provided by our structural comparison with previously characterized PGM family members. Genetic characterization of PGM2 in the rodent parasite Plasmodium berghei indicated that the protein might be essential to blood stage asexual growth, and a GFP tagged allele is expressed in both blood and zygote ookinete development and located in the cytoplasm. The P. falciparum PGM2 is either an enzyme implicated in the phosphate metabolism of the parasite or a regulator of its life cycle.

PubMed: 21689687
DOI: 10.1016/j.molbiopara.2011.06.001

Experimental method

X-RAY DIFFRACTION (2.01 Å)